Molecular characterization of the 2022 Sudan virus disease outbreak in Uganda.

IMPORTANCE: Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013-2016 Western Africa outbreak demonstrated how devastating EBOD can be when it reaches an urban population. Here, the 2022 Sudan virus disease (SVD) outbreak in Mubende District, Uganda, is summarized, and the genetic relatedness of the new variant is evaluated. The Mubende variant exhibited 96% amino acid similarity with historic SUDV sequences from the 1970s and a high degree of conservation throughout the outbreak, which was important for ongoing diagnostics and highly promising for future therapy development. Genetic differences between viruses identified during the Mubende SVD outbreak were linked with epidemiological data to better interpret viral spread and contact tracing chains. This methodology should be used to better integrate discrete epidemiological and sequence data for future viral outbreaks.

Development of a Scorecard to Monitor Progress toward National Cholera Elimination: Its Application in Uganda.

In 2017, the Global Task Force for Cholera Control (GTFCC) set a goal to eliminate cholera from ≥ 20 countries and to reduce cholera deaths by 90% by 2030. Many countries have included oral cholera vaccine (OCV) in their cholera control plans. We felt that a simple, user-friendly monitoring tool would be useful to guide national progress toward cholera elimination. We reviewed cholera surveillance data of Uganda from 2015 to 2021 by date and district. We defined a district as having eliminated cholera if cholera was not reported in that district for at least 4 years. We prepared maps to show districts with cholera, districts that had eliminated it, and districts that had eliminated it but then "relapsed." These maps were compared with districts where OCV was used and the hotspot map recommended by the GTFCC. Between 2018 and 2021, OCV was administered in 16 districts previously identified as hotspots. In 2018, cholera was reported during at least one of the four previous years from 36 of the 146 districts of Uganda. This number decreased to 18 districts by 2021. Cholera was deemed "eliminated" from four of these 18 districts but then "relapsed." The cholera elimination scorecard effectively demonstrated national progress toward cholera elimination and identified districts where additional resources are needed to achieve elimination by 2030. Identification of the districts that have eliminated cholera and those that have relapsed will assist the national programs to focus on addressing the factors that result in elimination or relapse of cholera.

COVID-19 and the law in Uganda: a case study on development and application of the public health act from 2020 to 2021.

BACKGROUND: Despite the discovery of vaccines, the control, and prevention of Coronavirus disease 2019 (COVID-19) relied on non-pharmaceutical interventions (NPIs). This article describes the development and application of the Public Health Act to implement NPIs for COVID-19 pandemic control in Uganda. METHODS: This is a case study of Uganda's experience with enacting COVID-19 Rules under the Public Health Act Cap. 281. The study assessed how and what Rules were developed, their influence on the outbreak progress, and litigation. The data sources reviewed were applicable laws and policies, Presidential speeches, Cabinet resolutions, statutory instruments, COVID-19 situation reports, and the registry of court cases that contributed to a triangulated analysis. RESULTS: Uganda applied four COVID-19 broad Rules for the period March 2020 to October 2021. The Minister of Health enacted the Rules, which response teams, enforcement agencies, and the general population followed. The Presidential speeches, their expiry period and progress of the pandemic curve led to amendment of the Rules twenty one (21) times. The Uganda Peoples Defense Forces Act No. 7 of 2005, the Public Finance Management Act No. 3 of 2015, and the National Policy for Disaster Preparedness and Management supplemented the enacted COVID-19 Rules. However, these Rules attracted specific litigation due to perceived infringement on certain human rights provisions. CONCLUSIONS: Countries can enact supportive legislation within the course of an outbreak. The balance of enforcing public health interventions and human rights infringements is an important consideration in future. We recommend public sensitization about legislative provisions and reforms to guide public health responses in future outbreaks or pandemics.

Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study.

Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19-0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53-5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54-1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.

Improving the effectiveness of Field Epidemiology Training Programs: characteristics that facilitated effective response to the COVID-19 pandemic in Uganda.

BACKGROUND: The global need for well-trained field epidemiologists has been underscored in the last decade in multiple pandemics, the most recent being COVID-19. Field Epidemiology Training Programs (FETPs) are in-service training programs that improve country capacities to respond to public health emergencies across different levels of the health system. Best practices for FETP implementation have been described previously. The Uganda Public Health Fellowship Program (PHFP), or Advanced-FETP in Uganda, is a two-year fellowship in field epidemiology funded by the U.S. Centers for Disease Control and situated in the Uganda National Institute of Public Health (UNIPH). We describe how specific attributes of the Uganda PHFP that are aligned with best practices enabled substantial contributions to the COVID-19 response in Uganda. METHODS: We describe the PHFP in Uganda and review examples of how specific program characteristics facilitate integration with Ministry of Health needs and foster a strong response, using COVID-19 pandemic response activities as examples. We describe PHFP activities and outputs before and during the COVID-19 response and offer expert opinions about the impact of the program set-up on these outputs. RESULTS: Unlike nearly all other Advanced FETPs in Africa, PHFP is delinked from an academic degree-granting program and enrolls only post-Master's-degree fellows. This enables full-time, uninterrupted commitment of academically-trained fellows to public health response. Uganda's PHFP has strong partner support in country, sufficient technical support from program staff, Ministry of Health (MoH), CDC, and partners, and full-time dedicated directorship from a well-respected MoH staff member. The PHFP is physically co-located inside the UNIPH with the emergency operations center (EOC), which provides a direct path for health alerts to be investigated by fellows. It has recognized value within the MoH, which integrates graduates into key MoH and partner positions. During February 2020-September 2021, PHFP fellows and graduates completed 67 major COVID-related projects. PHFP activities during the COVID-19 response were specifically requested by the MoH or by partners, or generated de novo by the program, and were supervised by all partners. CONCLUSION: Specific attributes of the PHFP enable effective service to the Ministry of Health in Uganda. Among the most important is the enrollment of post-graduate fellows, which leads to a high level of utilization of the program fellows by the Ministry of Health to fulfill real-time needs. Strong leadership and sufficient technical support permitted meaningful program outputs during COVID-19 pandemic response. Ensuring the inclusion of similar characteristics when implementing FETPs elsewhere may allow them to achieve a high level of impact.

Uganda National Institute of Public Health: Establishment and Experiences, 2013-2021.

Uganda is an ecological hot spot with porous borders that lies in several infectious disease transmission belts, making it prone to disease outbreaks. To prepare and respond to these public health threats and emergencies in a coordinated manner, Uganda established the Uganda National Institute of Public Health (UNIPH) in 2013.Using a step-by-step process, Uganda's Ministry of Health (MOH) crafted a strategy with a vision, mission, goal, and strategic objectives, and identified value additions and key enablers for success. A regulatory impact assessment was then conducted to inform the drafting of principles of the bill for legislation on the Institute.Despite not yet attaining legal status, the UNIPH has already achieved faster, smarter, and more efficient and effective prevention, detection, and response to public health emergencies. Successes include a more coordinated multisectoral, disciplined, and organized response to emergencies; appropriate, timely, and complete information receipt and sharing; a functional national lab sample and results transportation network that has enabled detection and confirmation of public health events within 48 hours of alert; appropriate response to a confirmed public health event in 24-48 hours; and real-time surveillance of endemic- and epidemic-prone diseases.In this article, we document success stories, lessons learned, and challenges encountered during the unique staged process used to develop the components of the UNIPH. The creation of an integrated disease control center has proven to yield better collaboration and synergies between different arms of epidemic preparedness and response.

Safety and efficacy of hydroxychloroquine for treatment of non-severe COVID-19 among adults in Uganda: a randomized open label phase II clinical trial.

BACKGROUND: Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. DESIGN: We conducted a randomized open label Phase II clinical trial from October-December 2020. METHODS: Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. RESULTS: Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. CONCLUSION: Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. TRIAL REGISTRATION:  NCT04860284.

Marburg virus disease outbreak in Kween District Uganda, 2017: Epidemiological and laboratory findings.

INTRODUCTION: In October 2017, a blood sample from a resident of Kween District, Eastern Uganda, tested positive for Marburg virus. Within 24 hour of confirmation, a rapid outbreak response was initiated. Here, we present results of epidemiological and laboratory investigations. METHODS: A district task force was activated consisting of specialised teams to conduct case finding, case management and isolation, contact listing and follow up, sample collection and testing, and community engagement. An ecological investigation was also carried out to identify the potential source of infection. Virus isolation and Next Generation sequencing were performed to identify the strain of Marburg virus. RESULTS: Seventy individuals (34 MVD suspected cases and 36 close contacts of confirmed cases) were epidemiologically investigated, with blood samples tested for MVD. Only four cases met the MVD case definition; one was categorized as a probable case while the other three were confirmed cases. A total of 299 contacts were identified; during follow- up, two were confirmed as MVD. Of the four confirmed and probable MVD cases, three died, yielding a case fatality rate of 75%. All four cases belonged to a single family and 50% (2/4) of the MVD cases were female. All confirmed cases had clinical symptoms of fever, vomiting, abdominal pain and bleeding from body orifices. Viral sequences indicated that the Marburg virus strain responsible for this outbreak was closely related to virus strains previously shown to be circulating in Uganda. CONCLUSION: This outbreak of MVD occurred as a family cluster with no additional transmission outside of the four related cases. Rapid case detection, prompt laboratory testing at the Uganda National VHF Reference Laboratory and presence of pre-trained, well-prepared national and district rapid response teams facilitated the containment and control of this outbreak within one month, preventing nationwide and global transmission of the disease.